The present invention relates to the composition of, and methods of producing, a coated chewing gum product containing an effective amount of a medicament. The inventive composition accelerates the absorption of the medicament through the oral mucosa.
It is of course known to provide active medicaments to individuals for various purposes. These medicaments can be used to treat diseases and as such are typically referred to as drugs or medicaments. Likewise, the drugs or medicaments can be used for preventive purposes. Still, it is known to provide medicaments to an individual for a variety of non-medical purposes including enhancing performance or maintaining health.
There are a great variety of such medicaments. These medicaments run the gamut from stimulants such as caffeine to drugs such as analgesics, tranquilizers, and cardiovascular products, as well as vitamins, minerals, and supplements. Some such medicaments are taken on an “as-needed” basis while other medicaments must be taken at regular intervals by the individual.
Typically, drugs or medicaments are administered parenterally or enterally. Of course, parenteral administration is the administration of the drug intravenously directly into the blood stream. Enteral refers to the administration of the drug into the gastrointestinal tract. In either case, the goal of the drug administration is to move the drug from the site of administration towards the systemic circulation.
Oral administration of drugs is by far the most common method of moving drugs towards systemic circulation. When administered orally, drug absorption usually occurs due to the transport across the membranes of the epithelial cells within the gastrointestinal tract. Absorption after oral administration is confounded by numerous factors. These factors include differences down the alimentary cannel in: the luminal pH; surface area per luminal volume; perfusion of tissue, bile, and mucus flow; and the epithelial membranes. See Merck Manual at page 2599.
A further issue affecting the absorption or orally administered drugs is the form of the drug. Most orally administered drugs are in the form of tablets or capsules. This is primarily for convenience, economy, stability, and patient acceptance. Accordingly, these capsules or tablets must be disintegrated or dissolved before absorption can occur. There are a variety of factors capable of varying or retarding disintegration of solid dosage forms. Further, there are a variety of factors that affect the dissolution rate and therefore determine the availability of the drug for absorption. See Merck Manual at page 2600.
When a drug rapidly dissolves from a drug product and readily across membranes, absorption from most site administration tends to be complete. This is not always the case for drugs given orally. Before reaching the vena cava, the drug must move down the alimentary canal and pass through the gut wall and liver, which are common sites of drug metabolism. Thus, the drug may be metabolized before it can be measured in the general circulation. This cause of a decrease in drug input is called the first pass effect. A large number of drugs show low bioavailabilities owning to an extensive first pass metabolism. The two other most frequent causes of low bioavailability are insufficient time in the GI tract and the presence of competing reactions. See Merck Manual at page 2602.
Bioavailability considerations are most often encountered for orally administered drugs. Differences in bioavailability can have profound clinical significance.
Although parenteral administration does provide a method for eliminating a number of the variables that are present with oral administration, parenteral administration is not a preferable route. Typically parenteral administration requires the use of medical personnel and is just not warranted nor practical for the administration of most agents and drugs, e.g., analgesics. Even when required, parenteral administration is objectionable due to patient concerns including comfort, infection, etc., as well as the equipment and costs involved.
It is known to incorporate medicaments into chewing gums for the purpose of providing an opportunity for the medicament to be absorbed through mucous membranes in the mouth. For example, U.S. Pat. No. 4,639,368 to Niazi discloses chewing gum compositions containing orally administrable medicament capable of being absorbed through the buccal cavity. Such systems have the advantage that the medicament is absorbed directly into the bloodstream. Increasing the rate of this absorption would further enhance the benefit of delivering medicaments using chewing gum.
Earlier patent applications owned by Applicants' assignee disclose such enhanced systems, which are more fully explored in the present application. It was earlier discovered that it is particularly advantageous to formulate a medicinal gum product as a coated chewing gum with a pharmaceutical agent in the coating to overcome the tendency for the agent to be entrapped in the gum base. Grandparent Application PCT/US99/29742, published as WO 00/35296, discloses adding an active agent to the coating of chewing gum. The active agent may be added to the coating solution and can be premixed with a flavor or solvent. The active agent may be added to the coating along with transdermal enhancing agents to increase transmucosal absorption.
Grandparent Application PCT/US99/29792, published as WO 00/35298, discloses a method for producing a chewing gum with a controlled release of an active agent by encapsulating the active agent. The use of sodium bicarbonate in a chewing gum containing a medicament, to increase the buccal/lingual absorption of the medicament into the bloodstream by raising the pH of the saliva, is also discussed.